Mismatch repair co-opted by hypermutation.
Mice homozygous for a disrupted allele of the mismatch repair gene Pms2 have a mutator phenotype. When this allele is crossed into quasi-monoclonal (QM) mice, which have a very limited B cell repertoire, homozygotes have fewer somatic mutations at the immunoglobulin heavy chain and lambda chain loci than do heterozygotes or wild-type QM mice. That is, mismatch repair seems to contribute to somatic hypermutation rather than stifling it. It is suggested that at immunoglobulin loci in hypermutable B cells, mismatched base pairs are "corrected" according to the newly synthesized DNA strand, thereby fixing incipient mutations instead of eliminating them.
Cascalho
M
M
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0670, USA.
Wong
J
J
Steinberg
C
C
Wabl
M
M
D000251:Adenosine Triphosphatases; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001482:Base Composition; D001483:Base Sequence; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006579:Heterozygote; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000737:chemistry / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000070976:Mismatch Repair Endonuclease PMS2; D008969:Molecular Sequence Data; D009154:Mutation; D011506:Proteins / Q000235:genetics* / Q000502:physiology
D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains; D011506:Proteins; D000251:Adenosine Triphosphatases; C499533:Pms2 protein, mouse; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes